Here We Go Again! Adenovirus 14: Another Emerging Pathogen

Abstract & Commentary

By Stan Deresinski, MD, FACP, Clinical Professor of Medicine, Stanford, Associate Chief of Infectious Diseases, Santa Clara Valley Medical Center, is Editor for Infectious Disease Alert.

Synopsis: Adenovirus 14 has emerged as a cause of severe respiratory infections in the United States.

Source: CDC. Acute respiratory disease associated with adenovirus serotype 14 — four states, 2006-2007. MMWR 2007; 56:1181-1184.

The death of a 12-day-old infant in New York City in May of 2006 was found to have been due to adenovirus serotype 14. Almost a year later, in April of 2007, the Oregon Public Health Division was notified of the occurrence of a number of cases of severe adenovirus pneumonia at a single hospital., leading to a retrospective examination of reports from several clinical laboratories in the state. This led to the identification of a total 68 patients with a positive test for adenovirus infection from November 2006 through April 2007. Of the 50 isolates available for testing, 31 (62%) were identified as serotype 14. Medical records of 30 patients with adenovirus 14 infection were available for review; the median age of the patients was 53.4 years (range, 2 weeks to 82 years); 73% were male. Approximately one-fifth occurred in children < 5 years of age, while all the remainder occurred in individuals > 18 years of age. Three-fourths were hospitalized, and one-half of the total required intensive care. Seven patients (23%) died. No epidemiological factors linking patients was identified. A comparison with 12 patients with adenovirus infection not due to serotype 14 found their median age was only 1.1 years, and only 2 required hospitalization, none in the ICU; none died.

In another occurrence, four residents of the same unit of a residential care facility, 3 with chronic obstructive lung disease and one with AIDS, were hospitalized with pneumonia due to adenovirus in May 2007; all 3 isolates available for testing were found to be serotype 14. Three patients required mechanical ventilation and one (the AIDS patient) died. No cases were identified in other residents or in staff.

A large outbreak of adenovirus in basic military trainees at Lackland Air Force Base in Texas began in early 2007, resulting in 27 pneumonia hospitalizations; 5 patients required ICU care and one died. Six of 218 health care workers (3%) had laboratory evidence of adenovirus 14 infection; 5 had had direct contact with at least one of the hospitalized patients. Cases have continued to occur among trainees, with 55 having onset during the week of September 23-29.

Commentary

Adenovirus is a non-enveloped, double-stranded DNA virus with 51 known serotypes. In addition to causing both lower and upper respiratory tract infections, it is a common cause of conjunctivitis (with most cases caused by serotypes 8, 19, and 37), gastroenteritis (types 40 and 41), and may also cause urinary tract infection (particularly in transplant patients). While cases occur throughout the year, there is a predominance of cases in the winter and spring.

While adenovirus 14 was first described in 1955, it has only been infrequently identified since an outbreak in military recruits in Spain in 1969, except for a report of infection in children in Taiwan in 2001-2002. Restriction enzyme analysis of viral genomic DNA has demonstrated that the type 14 strains from 3 military training camps belong to a novel subtype named 14a.1 The viral fiber protein contains cell receptor binding sites, and changes in these sites can alter adenovirus tissue tropism. In fact, when compared to a prototype type 14 strain, 14a has been found to have a deletion in the knob region of the fiber protein,1 a change that may have contributed to the changing epidemiology and, possibly, virulence of this virus.

Evidence from a survey of adenovirus isolates from 22 medical facilities in the United States from 2004-2006 suggests a very recent change in the epidemiology of adenovirus infections.2 In this study of 2237 isolates utilizing hexon gene sequencing, adenovirus type 14 was not among the 8 most frequently identified types. Only 3 (0.3%) cases of type 14 infection were identified among 936 nonimmunocompromised children < 7 years of age, and none were detected in 123 immunocompromised individuals of any age. There was, instead, a statistically significant increasing trend of detection of adenovirus type 21 over the time of the study. Multivariate analysis identified the following as independent risk factors for severe infection: age < 7 years, underlying chronic disease, recent transplantation, and adenovirus type 5 or type 21 infection — not type 14 infection.

Nonetheless, this report from the CDC makes it apparent that we are witnessing yet another evolutionary microbial event with the emergence of a strain of adenovirus which has caused severe disease in widespread geographic areas in the United States. This highlights the importance of the incorporation of effective viral diagnostics in the care of patients with infections, something that is sorely lacking at many health care facilities.

References

  1. Kajon AE, et al. Adenovirus 14 strain emerging in the United States in association with ILI and pneumonia exhibits a unique fiber knob sequence. 45th Annual Meeting of the Infectious Disease Society of America, October 4-7, 2007, San Diego, CA. Abstract 704.
  2. Gray GC, et al. Genotype prevalence and risk factors for severe clinical adenovirus infection, United States 2004-2006. Clin Infect Dis. 2007;45:1120-1131.